It is known that nateglinide [compound name: N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine] exhibits an excellent blood glucose-lowering effect by oral administration and therefore, is useful as a therapeutic agent for diabetes (Japanese Patent Publication No. Hei 4-15221).
On the other hand, the nateglinide is a poorly water soluble substance and therefore, capsules filled with nateglinide drug substance powder or ordinary tablets containing nateglinide do not dissolve well when administered orally because of its low disintegrating ability. As a result, such nateglinide-containing preparations can not show the fast-acting and short duration effect in decreasing a blood glucose level (fast-acting hypoglycemic agent), which is characteristic of nateglinide. In order to show the characteristic efficacy of nateglinide, the drug needs to be released rapidly from preparations and so improvement on a preparation has been required.
As methods for solving the problem, there has been provided a preparation wherein a low-substituted hydroxypropylcellulose is incorporated as a disintegrant (Japanese Patent No. 2508949).
Meanwhile, nateglinide has crystal polymorphs. Such a method wherein the disintegrant is incorporated into the preparation effectively enhance in disintegrating ability and increase in the dissolution rate of the preparation containing nateglinide in stable H-type crystal form and semi-stable crystal form. However, it can not be regarded as effective in all crystal forms of nateglinide.
Besides, when the nateglinide in crystal forms other than the most stable H-type crystal forms and the semi-stable crystal forms are used, it is known that crystal transition happens during producing or conserving preparations. It is generally preferred that crystal transition of drugs does not happen during producing or conserving pharmaceutical preparations.